This invention relates to compositions containing naturally occurring or synthetic taxanes or taxoids. Compositions of the present invention can be used to treat epidermal lesions, such as those resulting from viral or microbial infections.
The herpes simplex viruses, including HSV-1 (oro-facial) and HSV-2 (genital herpes), present a serious problem for millions of people worldwide. To the best of applicant""s knowledge, until now, an effective, economical, and readily available topical treatment has not existed.
Herpes simplex virus is a common, recurrent, and chronic infection. It is estimated that at least 75% of the world""s population has been infected with HSV-1 and more than 20% with HSV-2. Although the majority of cases are asymptomatic, chronic outbreaks of lesions are very common, usually occurring in mucous membrane areas and the surrounding skin. The most common of these lesions occur on the lips or face and are commonly referred to as xe2x80x9ccold soresxe2x80x9d or xe2x80x9cfever blistersxe2x80x9d. Genital herpes lesions occur on the genitals and buttocks and are particularly troubling because of their possible role in contributing to the spread of HIV.
Herpes lesions first appear as an area of irritation (an itching or burning sensation) known as the prodromal stage. Within a few hours, these lesions develop into small vesicles or blisters. Typically, these vesicles soon rupture and form shallow ulcerations which may scab over and heal in about ten to twenty days. The ruptured vesicles may also cause secondary infections and spread the virus to the surrounding tissue.
After initial exposure to the herpes simplex virus, the host develops antibodies that can maintain the virus in a latent state. Despite the presence of antibodies, the latent virus may be reactivated by stress, exposure to sunlight, fever, hormonal changes, menstruation, and trauma. Eruptions can occur randomly and may persist for weeks.
Paclitaxel, perhaps the most familiar of the taxanes, was first isolated in 1971 from the bark of Taxus brevifolia, commonly known as the Pacific Yew, and was approved in 1992 by the US Food and Drug Administration for treatment of metastatic ovarian cancer and later for breast cancer. Its mechanism of action is believed to involve promoting formation and hyperstabilization of microtubules, thereby preventing the disassembly of microtubules necessary for completion of cell division. It also has been reported that paclitaxel induces expression of cytokines, affects the activity of kinases and blocks processes essential for metastasis, in as yet uncharacterized mechanisms of action.
Paclitaxel has attracted unusually strong scientific attention, not only because of its unique antiproliferative mechanism of action, but also because it is active against nearly all cancers against which it has been tested, and because it has been discovered to be an analog of numerous, closely-related compounds occurring naturally. Taxanes are now recognized as a new class of anticancer compounds.
Research supported in part by the National Institute of Allergy and Infectious Diseases (NIAID), and conducted by virologists at the University of Chicago and the University of Alabama, has demonstrated that compounds extracted from the yew tree possess clinically significant anti-viral properties that specifically inhibit replication of HSV-1 and HSV-2 in vitro.
There is currently no known cure for herpes simplex virus infections. However, a topical therapy that delivers clinically-demonstrated, anti-viral compositions to the affected area, inhibiting viral replication in the lesions, accelerating healing of the existing lesion, and preventing the spread of secondary infections, would be of enormous benefit to the herpes sufferer.
The present invention provides compositions and methods for treating diseased, biological tissue, such as the epidermis, in a mammal. Compositions of the present invention can be used to treat epidermal lesions, such as those resulting from viral infections including, but not limited to: herpes viruses, varicella zoster virus (VZV), cytomegalovirus (CMV), Epstein-Barr virus (EBV), and papillomavirus. Compositions of the present invention can also be used to treat epidermal lesions, ulcerations, abrasions, inflammation and other conditions resulting from microbial infections. In particular, compositions of the present invention are especially adapted to treat lesions caused by herpes viruses.
In one embodiment, the present invention provides compositions useful for treating diseased, biological tissue, such as the epidermis, in a mammal. The compositions of the present invention are effective in treating viral infections, bacterial infections and inflammation. The compositions of the present invention include at least one taxane. The taxane can be a semi-synthetic taxane, such as the commercially-available taxane preparation marketed under the trademark Taxol(copyright), or can be an entirely synthetic taxane that is chemically synthesized by any means known to those skilled in the art. Additionally, the taxane can be derived from a natural source, such as from the needles and branches of any member of the yew family (Taxaceae), such as the Pacific Yew tree (Taxus brevifolia), T. baccata, T. wallichiana, T. cuspiduta, T. canadensis, T. floridana, and others, as well as from the fungal endophyte Taxomyces andreanae. Preferably, compositions of the present invention include at least one taxane in an amount of from about 0.005% to about 10% of the total weight of the composition. Preferably, the compositions of the present invention also include a natural oil such as, but not limited to, olive oil, mineral oil, corn oil, sunflower oil, peanut oil, and fish oil. Preferably, the compositions of the present invention also contain a wax such as, but not limited to, beeswax, U.S.P. Carbowax 5000(copyright), U.S.P. Carbowax 600(copyright) (the foregoing Carbowax(copyright) products are manufactured by Union Carbide Corporation, World Headquarters, 39 Old Ridgebury Road, Danbury, Conn. 06817-001) and petrolatum.
A presently preferred composition of the present invention is formed from an extract from the Pacific Yew tree (Taxus brevifolia) combined with virgin olive oil and beeswax. The T. brevifolia extract is prepared as described in Example 1 herein and combined with olive oil at a ratio of about 1:1 and the ethanol (utilized in the extraction of the T. brevifolia tissue) and water (from the extract) are completely evaporated before the combination of T. brevifolia extract and olive oil is further combined with the beeswax at a ratio of about 6:1. Preferably, the compositions of the present invention are topically applied in the form of an ointment or salve to the site of disease.
In addition to the foregoing components, compositions of the present invention can include additional ingredients including, but not limited to, analgesics and anesthetics.
In another embodiment, the present invention includes a method of treating diseased biological tissue, such as the epidermis, in a mammal. The method of the present invention includes the step of contacting a diseased biological tissue, such as the epidermis, with a composition of the present invention containing an amount of a taxane, taxoid, or related compound, that is effective to ameliorate the disease symptoms. The methods and compositions of the present invention are effective in treating viral infections, bacterial infections and inflammation. Examples of viral infections that can be treated using the compositions and method of the present invention include, but are not limited to, herpes viruses, varicella zoster virus (VZV), cytomegalovirus (CMV), Epstein-Barr virus (EBV), and papillomavirus.